Chromogranin A and the tumor microenvironment

Abstract

Chromogranin A (CgA) is an acidic glycoprotein belonging to a family of regulated secretory proteins stored in the dense core granules of the adrenal medulla and of many other neuroendocrine cells and neurons. This protein is frequently used as a diagnostic and prognostic serum marker for a range of neuroendocrine tumors. Circulating CgA is also increased in patients with other diseases, including subpopulations of patients with non-neuroendocrine tumors, with important prognostic implications. A growing body of evidence suggests that CgA is more than a diagnostic/prognostic marker for cancer patients. Indeed, results of in vitro experiments and in vivo studies in animal models suggest that this protein and its fragments can affect several elements of the tumor microenvironment, including fibroblasts and endothelial cells. In this article, recent findings implicating CgA as a modulator of the tumor microenvironment and suggesting that abnormal secretion of CgA could play important roles in tumor progression and response to therapy in cancer patients are reviewed and discussed.

Fig. 1

Sequence alignment of CgA and EBP50 of different species. The conserved residues in the region 47–66, critical for binding to fibroblast membrane, are shown in bold. The conserved residues in the AKERAHQ region of CgA (critical for the pro-adhesive activity of VS-1) and of EBP50 (cross-reactive with anti-human CgA antibodies) are underlined